Effects of exercise training on the cardiovascular system: Pharmacological approaches

doi:10.1016/j.pharmthera.2007.03.010

Pharmacology & Therapeutics

Volume 114, Issue 3, June 2007, Pages 307-317

https://doi.org/10.1016/j.pharmthera.2007.03.010 Get rights and content

Abstract

Physical exercise promotes beneficial health effects by preventing or reducing the deleterious effects of pathological conditions, such as arterial hypertension, coronary artery disease, atherosclerosis, diabetes mellitus, osteoporosis, Parkinson's disease, and Alzheimer disease. Human movement studies are becoming an emerging science in the epidemiological area and public health. A great number of studies have shown that exercise training, in general, reduces sympathetic activity and/or increases parasympathetic tonus either in human or laboratory animals. Alterations in autonomic nervous system have been correlated with reduction in heart rate (resting bradycardia) and blood pressure, either in normotensive or hypertensive subjects. However, the underlying mechanisms by which physical exercise produce bradycardia and reduces blood pressure has not been fully understood. Pharmacological studies have particularly contributed to the comprehension of the role of receptor and transduction signaling pathways on the heart and blood vessels in response to exercise training. This review summarizes and examines the data from studies using animal models and human to determine the effect of exercise training on the cardiovascular system.

Introduction

A healthy lifestyle has been strongly associated with the practice of regular physical activity. Evidence has shown that physically active subjects have more longevity with reduction of morbidity and mortality. Physical exercise prevents or reduces the deleterious effects of pathological conditions, such as arterial hypertension, coronary artery disease, atherosclerosis, diabetes mellitus, osteoporosis, Parkinson's disease, and Alzheimer disease (Kingwell, 2000, Sutoo and Akiyama, 2003, Larson and Wang, 2004). Classical kinetic studies were based exclusively in sports performance, but at present human movement studies are becoming an emerging science in the epidemiological area and public health.

Physical training produces significant alterations in autonomic nervous system activity and/or changes in cellular function resulting in marked modifications of the cardiovascular system function (Krieger et al., 1998, Kingwell, 2000). Basic sciences, such as physiology and biochemistry, have helped to increase knowledge in the physical exercise field and its association with cardiovascular benefits. Additionally, pharmacological studies have greatly contributed to the comprehension of the role of receptor and transduction pathways in the heart and blood vessels in response to exercise training. This review summarizes and examines the data from studies using animal models and human to determine the effect of exercise training on the cardiovascular system.

Section snippets

Adrenergic and muscarinic receptors and exercise training

The effect of exercise training on the sympathetic and parasympathetic activities has been studied in great detail by different groups (Frick et al., 1967, Lin and Horvath, 1972, Scheuer and Tipton, 1977, Katona et al., 1982, Geenen et al., 1988, Negrão et al., 1992, Grassi et al., 1994, Moore and Korzick, 1995, Shi et al., 1995, Collins and DiCarlo, 1997, Krieger et al., 1998, O'Sullivan and Bell, 2000). In general, these studies have shown that exercise training reduces sympathetic activity

Muscarinic cholinergic receptors and exercise

Acetylcholine released from parasympathetic fibers can stimulate 2 major types of receptors, named nicotinic and muscarinic receptors. Muscarinic receptors belong to the class of G protein-coupled receptor and are widely distributed throughout the periphery and the central nervous system (Caulfield, 1993). Five subtypes of muscarinic cholinergic receptors have been detected by molecular cloning, named M₁, M₂, M₃, M₄, and M₅. In cardiac tissue, the stimulation of the subtype M₂ muscarinic

Adenosine receptors and physical training

Adenosine is a nucleotide derived from ATP breakdown that exerts a variety of physiological actions in cardiovascular, renal, pulmonary, and immune systems (Ralevic & Burnstock, 1998). Specifically, in cardiovascular function, adenosine promotes vasodilatation and negative chronotropic and inotropic effects in several species (Berne, 1963, West and Belardinelli, 1985, Olsson and Pearson, 1990). At least 4 subtypes of adenosine receptors are found in the heart, namely A₁, A_2a, A_2b, and A₃

Responsiveness of vascular smooth muscle and exercise training

Originally, Furchgott and Zawadzki (1980) discovered that endothelial cells release a vascular smooth muscle relaxing factor that was named endothelium-derived releasing factor (EDRF). Later, Ignarro et al. (1987) and Palmer et al. (1987) revealed that EDRF was nitric oxide (NO; or a related compound) that is synthesized from the amino acid l-arginine by the enzyme NO synthase (NOS). Three isoforms of NOS, termed endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) have been

Erectile dysfunction and exercise

Erectile dysfunction is a public health problem, and it is now established that some vascular diseases such as hypercholesterolemia, diabetes mellitus, and arterial hypertension can interfere with the intricate vascular mechanisms underlying normal erection. Thus, alterations of penile arterial cell function may be the basis for the understanding of the prevalence of erectile dysfunction. Penile erection is a neurovascular phenomenon that requires dilation of penile vasculature, relaxation of

Summary and conclusion

Regular physical exercise is currently an important intervention to prevent and/or to manage cardiovascular diseases and other disorders. Specifically, the beneficial cardiovascular effects of physical training have been associated with alterations in autonomic nervous system and endothelial cells. However, the exact mechanisms by which physical exercise produces these alterations are not fully understood. Several pharmacological studies have been performed to investigate the effect of exercise

Acknowledgment

A. Zanesco and E. Antunes are supported by grants from the Fundação de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP).

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Associate editor: BrainEffects of exercise training on the cardiovascular system: Pharmacological approaches

Abstract

Introduction

Section snippets

Adrenergic and muscarinic receptors and exercise training

Muscarinic cholinergic receptors and exercise

Adenosine receptors and physical training

Responsiveness of vascular smooth muscle and exercise training

Erectile dysfunction and exercise

Summary and conclusion

Acknowledgment

Am J Hypert

Prog Cardiovasc Dis

Pharmacol Ther

Urology

Trends Pharmacol Sci

Eur J Pharmacol

Eur J Pharmacol

Pharmacol Ther

Biochem Biophys Res Commun

J Biol Chem

Biochem Pharmacol

Biochim Biophys Acta

Int J Cardiol

Mol Aspects Med

Prog Cardiovasc Dis

J Mol Cell Cardiol

J Auton Nerv Syst

ACSM Position stand on the recommended quantaty and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in adults

Med Sci Sports Exerc

A study of adrenergic receptors

Am J Physiol

Pharmacology of penile erection

Pharmacol Rev

Plasma oxidative stress biomarkers, nitric oxide and heat shock protein 70 in trained elite soccer players

Eur J Appl Physiol

Cardiac nucleotide in hypoxia: possible role in regulation of coronary blood flow

Am J Physiol

G proteins in signal transduction

Annu Rev Pharmacol Toxicol

Exercise increases systemic nitric oxide production in men

J Cardiovasc Risk

Intensive training and cardiac autonomic control in high levl athletes

Med Sci Sports Exerc

Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases

Am J Physiol Cell Physiol

Cardiac beta-adrenergic receptors

ISI Atlas Sci Pharmacol

Isolated heart responsiveness to β-stimulation after exercise training in obesity

Med Sci Sports Exerc

Increase of anti-oxidant by exercise in the liver of obese Zucher rats

Clin Exp Pharmacol Physiol

Exercise training increases acetylcholine-stimulated endothelium-derived nitric oxide release in spontaneously hypertensive rats

J Biomed Sci

Daily exercise enhances acetylcholine-induced dilation in mesenteric and hindlimb vasculature of hypertensive rats

Clin Exp Hypertens

Phenyleprine-induced vasoconstriction of the rat superior mesenteric artery is decreased after repeated swimming

J Smooth Muscle Res

Exercise training enhances relaxation of the isolated guinea-pig saphenous artery in response to acetylcholine

Exp Physiol

Protective effect of prior physical conditioning on relaxing response of corpus cavernosum from rats made hypertensive by nitric oxide inhibition

Int J Impot Res

Daily exercise attenuates the sympathetic component of the arterial baroreflex control of heart rate

Am J Physiol

Adenosine receptor subtypes

Trends Pharmacol Sci

Overexpression of A3 adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts

Am J Physiol

Shear stress regulates endothelial nitric oxide synthase expression through c-Src by divergent signaling pathways

Circ Res

Role of c-Src in regulationof endothelial nitric oxide synthase expression during exercise training

Am J Physiol Heart Circ Physiol

Time course of enhanced endothelium-mediated dilation in aorta of trained rats

Med Sci Sports Exerc

Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation

Nature

Antagonist binding profiles of five cloned human muscarinic receptor subtypes

J Pharmacol Exp Ther

Free radicals in the physiological control of cell function

Physiol Rev

Associate editor: Brain
Effects of exercise training on the cardiovascular system: Pharmacological approaches

Molecular characterization of the human β₃-adrenergic receptor